COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Changes in Cannabis Consumption During the Global COVID-19 Lockdown: The International COVISTRESS Study

Introduction: COVID-19 lockdown measures have been sources of both potential stress and possible psychological and addiction complications. A lack of activity and isolation during lockdown are among the factors thought to be behind the growth in the use of psychoactive substances and worsening addictive behaviors. Previous studies on the pandemic have attested to an increase in alcohol consumption during lockdowns. Likewise, data suggest there has also been a rise in the use of cannabis, although it is unclear how this is affected by external factors. Our study used quantitative data collected from an international population to evaluate changes in cannabis consumption during the lockdown period between March and October, 2020. We also compared users and non-users of the drug in relation to: (1) socio-demographic differences, (2) emotional experiences, and (3) the information available and the degree of approval of lockdown measures. Methods: An online self-report questionnaire concerning the lockdown was widely disseminated around the globe. Data was collected on sociodemographics and how the rules imposed had influenced the use of cannabis and concerns about health, the economic impact of the measures and the approach taken by government(s). Results: One hundred eighty two respondents consumed cannabis before the lockdown vs. 199 thereafter. The mean cannabis consumption fell from 13 joints per week pre-lockdown to 9.75 after it (p < 0.001). Forty-nine respondents stopped using cannabis at all and 66 admitted to starting to do so. The cannabis users were: less satisfied with government measures; less worried about their health; more concerned about the impact of COVID-19 on the economy and their career; and more frightened of becoming infected in public areas. The risk factors for cannabis use were: age (OR = 0.96); concern for physical health (OR = 0.98); tobacco (OR = 1.1) and alcohol consumption during lockdown (OR = 1.1); the pre-lockdown anger level (OR = 1.01); and feelings of boredom during the restrictions (OR = 1.1). Conclusion: In a specific sub-population, the COVID-19 lockdown brought about either an end to the consumption of cannabis or new use of the drug. The main risk factors for cannabis use were: a lower age, co-addictions and high levels of emotions.publishedVersio

Four-days-a-week antiretroviral maintenance therapy in virologically controlled HIV-1-infected adults: the ANRS 162-4D trial

International audienceBackground:Intermittent treatment could improve the convenience, tolerability and cost of ART, as well as patients' quality of life. We conducted a 48 week multicentre study of a 4-days-a-week antiretroviral regimen in adults with controlled HIV-1-RNA plasma viral load (VL).Methods:Eligible patients were adults with VL  90%, with a power of 87% and a 5% type 1 error. The study was registered with ClinicalTrials.gov (NCT02157311) and EudraCT (2014-000146-29).Results:One hundred patients (82 men), median age 47 years (IQR 40-53), were included. They had been receiving ART for a median of 5.1 (IQR 2.9-9.3) years and had a median CD4 cell count of 665 (IQR 543-829) cells/mm3. The ongoing regimen included PI/r in 29 cases and NNRTI in 71 cases. At 48 weeks, 96% of participants (95% CI 90%-98%) had no failure while remaining on the 4-days-a-week regimen. Virological failure occurred in three participants, who all resumed daily treatment and became resuppressed. One participant stopped the strategy. No severe treatment-related events occurred.Conclusions:Antiretroviral maintenance therapy 4 days a week was effective for 48 weeks in 96% of patients, leading to potential reduction of long-term toxicities, high adherence to the antiretroviral regimen and drug cost saving

COVID‐19 lockdown consequences on body mass index and perceived fragility related to physical activity: A worldwide cohort study

International audienceBackground: This paper is a follow-up study continuing the COVISTRESS network previous research regarding health-related determinants.Objective: The aim was to identify the main consequences of COVID-19 lockdown on Body Mass Index and Perceived Fragility, related to Physical Activity (PA), for different categories of populations, worldwide.Design: The study design included an online survey, during the first wave of COVID-19 lockdown, across different world regions.Setting and participants: The research was carried out on 10 121 participants from 67 countries. The recruitment of participants was achieved using snowball sampling techniques via social networks, with no exclusion criteria other than social media access.Main outcome measures: Body Mass Index, Physical Activity, Perceived Fragility and risk of getting infected items were analysed. SPSS software, v20, was used. Significance was set at P < .05.Results: Body Mass Index significantly increased during lockdown. For youth and young adults (18-35 years), PA decreased by 31.25%, for adults (36-65 years) by 26.05% and for the elderly (over 65 years) by 30.27%. There was a high level of Perceived Fragility and risk of getting infected for female participants and the elderly. Correlations between BMI, Perceived Fragility and PA were identified.Discussion and conclusions: The research results extend and confirm evidence that the elderly are more likely to be at risk, by experiencing weight gain, physical inactivity and enhanced Perceived Fragility. As a consequence, populations need to counteract the constraints imposed by the lockdown by being physically active

The major worldwide stress of healthcare professionals during the first wave of the COVID-19 pandemic - the international COVISTRESS survey

IntroductionThe COVID-19 pandemic has initiated an upheaval in society and has been the cause of considerable stress during this period. Healthcare professionals have been on the front line during this health crisis, particularly paramedical staff. The aim of this study was to assess the high level of stress of healthcare workers during the first wave of the pandemic.Materials and methodsThe COVISTRESS international study is a questionnaire disseminated online collecting demographic and stress-related data over the globe, during the pandemic. Stress levels were evaluated using non-calibrated visual analog scale, from 0 (no stress) to 100 (maximal stress).ResultsAmong the 13,537 individuals from 44 countries who completed the survey from January to June 2020, we included 10,051 workers (including 1379 healthcare workers, 631 medical doctors and 748 paramedical staff). The stress levels during the first wave of the pandemic were 57.8 33 in the whole cohort, 65.3 +/- 29.1 in medical doctors, and 73.6 +/- 27.7 in paramedical staff. Healthcare professionals and especially paramedical staff had the highest levels of stress (p &lt; 0.001 vs non-healthcare workers). Across all occupational categories, women had systematically significantly higher levels of work-related stress than men (p &lt; 0.001). There was a negative correlation between age and stress level (r = -0.098, p &lt; 0.001). Healthcare professionals demonstrated an increased risk of very-high stress levels (&gt;80) compared to other workers (OR = 2.13, 95% CI 1.87-2.41). Paramedical staff risk for very-high levels of stress was higher than doctors' (1.88, 1.50-2.34). The risk of high levels of stress also increased in women (1.83, 1.61-2.09; p &lt; 0.001 vs. men) and in people aged &lt;50 (1.45, 1.26-1.66; p &lt; 0.001 vs. aged &gt;50).ConclusionsThe first wave of the pandemic was a major stressful event for healthcare workers, especially paramedical staff. Among individuals, women were the most at risk while age was a protective factor

Impact on disease mortality of clinical, biological, and virological characteristics at hospital admission and overtime in COVID‐19 patients

International audienc

Paediatric COVID-19 mortality: a database analysis of the impact of health resource disparity

Background The impact of the COVID-19 pandemic on paediatric populations varied between high-income countries (HICs) versus low-income to middle-income countries (LMICs). We sought to investigate differences in paediatric clinical outcomes and identify factors contributing to disparity between countries.Methods The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) COVID-19 database was queried to include children under 19 years of age admitted to hospital from January 2020 to April 2021 with suspected or confirmed COVID-19 diagnosis. Univariate and multivariable analysis of contributing factors for mortality were assessed by country group (HICs vs LMICs) as defined by the World Bank criteria.Results A total of 12 860 children (3819 from 21 HICs and 9041 from 15 LMICs) participated in this study. Of these, 8961 were laboratory-confirmed and 3899 suspected COVID-19 cases. About 52% of LMICs children were black, and more than 40% were infants and adolescent. Overall in-hospital mortality rate (95% CI) was 3.3% [=(3.0% to 3.6%), higher in LMICs than HICs (4.0% (3.6% to 4.4%) and 1.7% (1.3% to 2.1%), respectively). There were significant differences between country income groups in intervention profile, with higher use of antibiotics, antivirals, corticosteroids, prone positioning, high flow nasal cannula, non-invasive and invasive mechanical ventilation in HICs. Out of the 439 mechanically ventilated children, mortality occurred in 106 (24.1%) subjects, which was higher in LMICs than HICs (89 (43.6%) vs 17 (7.2%) respectively). Pre-existing infectious comorbidities (tuberculosis and HIV) and some complications (bacterial pneumonia, acute respiratory distress syndrome and myocarditis) were significantly higher in LMICs compared with HICs. On multivariable analysis, LMIC as country income group was associated with increased risk of mortality (adjusted HR 4.73 (3.16 to 7.10)).Conclusion Mortality and morbidities were higher in LMICs than HICs, and it may be attributable to differences in patient demographics, complications and access to supportive and treatment modalities

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Background: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83-7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97-2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14-1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25-1.30]). Conclusions: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Background: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83–7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97–2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14–1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25–1.30]). Conclusions: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable